The human spine consists of thirty-three vertebral bodies of which the distal nine are fused to form the sacrum and coccyx (Simon, S R, et al 1994; Bogduk, N., 1997). The 24 vertebrae, with the exception of C1 and C2, are each separated by an intervertebral disc (IVD). The IVD anchors adjacent vertebral bodies and by doing so allows for spinal stabilization, load bearing, and movement. The intervertebral disc is a specialized structure consisting of two interdependent tissues, the annulus fibrosus (AF) and the nucleus pulposus (NP) which merge with the cartilage endplate (Bogduk, N., 1997; Eyre, D R, 1979). The composition of the AF and nucleus pulposus varies with anatomical site in the tissue and the age of the individual (Eyre, D R, 1979; Buckwalter, 1995). The normal function of the disc is dependent on maintenance of the composition, organization, and integrity of the different components (Chiba, 1998). The annulus fibrosus is responsible for withstanding circumferential tensile forces, while the nucleus pulposus resists compressive forces during normal activity (Simon, 1994; Bogduk, 1997; Eyre, 1979; Buckwalter, 1995). The disc is relatively avascular as only the outer portion of the annulus contains blood vessels in adults (Buckwalter, 1995). The disc cells rely on diffusion of nutrients from these vessels and from blood vessels in the vertebral body.
The annulus fibrosus surrounds the nucleus pulposus and consists of approximately 10-20 lamellar sheets each composed of collagen fibres oriented parallel to each other and about 65° from the vertical. Although the angle is the same, the direction of the inclination alternates with each sheet such that the fibres in one lamella are 65° to the right, while in the next lamella they are 65° to the left. Every second lamella has the same orientation (Bogduk, N., 1997). This very specific collagen organization allows the disc to rotate and flex. Collagen makes up about 70% of the dry weight of the annulus (Buckwalter, 1995). Type I collagen is the predominate collagen, but types II, III, V, VI and type IX collagen are also present in lesser amounts (Bogduk, N., 1997; Buckwalter, 1995; Nerlich, 1998). The average diameter of the collagen fibril is 50-60 nm as determined by transmission electron microscopy (Eyre, 1979). The annulus also contains a small amount of proteoglycans and these also have a specific distribution. The proteoglycan content in the tissue is lowest in the periphery of the annulus fibrosus and increases in amount towards the nucleus pulposus (Bogduk, N., 1997). The major proteoglycan is aggrecan (Bogduk, N., 1997; Inerot, 1991; Roberts, 1994; Antoniou, 1996; and Sztrolovics, 1997). Small proteoglycans such as decorin, biglycan, and fibromodulin are also present (Gotz, 1997; Sztrolovics, 1999). Elastin and other non-collagenous proteins are detected in the disc (Bogduk, 1997). The cellularity across the annulus varies, as it is more cellular in the outer third (0.7 μg DNA/gm dry weight) when compared to the inner two-thirds (0.1 μg DNA/gm dry weight) of the annulus (Bayliss, 1998).
The nucleus pulposus (NP) is gelatinous type tissue, which is surrounded by the annulus fibrosus and confined by the cartilagenous endplates of the vertebral bodies (Bogduk, 1997). It consists of proteoglycans within a loose network of collagen and does not show the same degree of collagen organization in the matrix as the annulus fibrosus (Eyre, 1979; Aguiar, 1999). Proteoglycans comprise approximately up to 65% of the dry weight of the nucleus. Aggrecan is the major proteoglycan present in the nucleus pulposus and about 60% of it is present in a form that does not aggregate. Other proteoglycans, such as decorin, biglycan, and fibromodulin, are also present (Buckwalter, 1995; Gotz, 1997; Sztrolovics, 1999; and Oegema, 1993). The nucleus pulposus contains predominately type II collagen but there are other collagen types present, such as III, VI, IX, and XI (Eyre, 1979; Buckwalter, 1995; Aulisa, 1998). Type I collagen has been detected in small amounts in the nucleus pulposus of humans (Eyre, 1979) and rats (Rufai, 1995). The average diameter of the collagen fibrils is around 30 nm as determined by transmission electron microscopy (Eyre, 1979). In childhood, the nucleus contains notochordal cells but these disappear with age. It has been postulated that these cells contribute to the maintenance of the nucleus pulposus and their absence in the adult disc explains the high prevalence of disc degeneration (Aguiar, 1999).
The other component of the disc is the cartilage endplate, a thin layer of articular cartilage that is integrated with the underlying bone of the vertebral body (Bogduk, 1997). As the endplate covers a portion of the vertebral body it confines the nucleus pulposus entirely but only a portion of the annulus fibrosus. The peripheral portion of the annulus fibrosus inserts directly into the bone. The endplate is considered part of the disc as it can easily be separated from the vertebral body (Bogduk, 1997). Like articular cartilage, the endplate consists predominately of water, proteoglycans and collagen (Bogduk, 1997; Antoniou, 1996). The zone of tissue closer to the bone is richer in collagen as compared to the zone closer to the nucleus pulposus, which contains less collagen and more proteoglycans and water (Bogduk, 1997).
Intervertebral disc prolapse is a very common problem and currently there is no optimal treatment for persistent disease. In an autopsy study, 97% of individuals 50 years or older showed disc degeneration (Miller, 1988). It is not known why it is so common, but may be due in part to the relative avascularity of the tissue until there is prolapse (Ozaki, 1999), mechanical factors (Hadjipavlou, 1999), the absence of notochordal cells (Aguiar, 1999) or genetic factors (Kawaguchi, 1999). The back pain that can develop as a result of this disease is often self-limited, but a percentage of affected individuals require surgery (Kraemer, 1994; Borenstein, 1999). Although the surgical intervention may relieve pain faster, this procedure does not restore disc height or its original load bearing capacity. Post-discotomy syndrome, which is characterized by persistent pain and occurs after disc surgery, may be treated by spinal fusion. This is a less than optimal treatment as it is not always successful and results in limited flexibility and degenerative changes in adjacent vertebrae (Javedan, 1999).
IVD replacement, with allografts or prosthetic devices, has been attempted but met with limited success (Leivseth, 1999; Hou, 1991; Enker 1993; Bao, 1996; and Kostiuk, 1997). Alternative treatments such as laser treatment are now being studied (Zeegers, 1999). Intraspinal injection of chymopapain has been used; however, a recent study of 51 patients showed that this treatment had no effect (Choy, 1998). Although not used currently, gene therapy may be another way to treat this disease (Nishida, 1998; Nishida, 1999; and Evans & Robbins, 1999). There is clearly a need to develop novel approaches to the treatment of disc disease.